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Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide and its prognosis is highly heterogeneous, being related not only to tumour burden but also to the severity of underlying chronic liver disease. Moreover, advances in systemic therapies for HCC have increased the complexity of patient management. Randomised-controlled trials represent the gold standard for evidence generation across all areas of medicine and especially in the oncology field, as they allow for unbiased estimates of treatment effect without confounders. Observational studies have many problems that could reduce their internal and external validity. However, large prospective (well-conducted) observational real-world studies can detect rare adverse events or monitor the occurrence of long-term adverse events. How best to harness real world data, which refers to data generated from the routine care of patients, and real-world 'evidence', which is the evidence generated from real-world data, represents an open challenge. In this review article, we aim to provide an overview of the benefits and limitations of different study designs, particularly focusing on randomised-controlled trials and observational studies, to address important and not fully resolved questions in HCC research., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Current recommendations for the surveillance of HCC are based on the semiannual liver ultrasound (with or without serum alpha-fetoprotein) in patients with cirrhosis and in subgroups with chronic hepatitis B infection. However, the sensitivity of this strategy is suboptimal for the detection of early-stage tumors, especially in obese patients, due to interoperator variability and poor adherence. The detection rate of focal liver lesions is excellent with MRI, making it the best alternative candidate for surveillance. However, performing a full contrast-enhanced MRI is unrealistic because of limited availability and health economics. Abbreviated MRI (AMRI) corresponds to the acquisition of a limited number of sequences with a high detection rate. The theoretical benefits of AMRI are a reduced acquisition time (≤10 min) with improved time-effectiveness and cost-effectiveness compared with conventional MRI, and greater accuracy than ultrasound. Numerous protocols may be performed, including T1-weighted, T2-weighted, and DWI sequences, with or without contrast administration. Although published studies report promising per-patient results, they should be interpreted with caution. Indeed, most studies were simulated, retrospectively reviewing a subset of sequences in relatively small populations who underwent a full MRI. They also included groups that were not representative of screening populations. In addition, most were published by Asian groups, with at-risk populations that were different from Western populations. There are no existing longitudinal studies that directly compare the different AMRI approaches or AMRI to ultrasound. Finally, it is possible that 1 approach will not fit all patients and that strategies should be tailored to the risk of HCC, in particular in relation to the cost and availability of AMRI. Several trials are ongoing to evaluate these questions., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background & Aims: The diagnostic accuracy of Liver Imaging Reporting and Data System (LI-RADS) v.2018 and European Association for the Study of the Liver (EASL) criteria for the diagnosis of HCC have been widely evaluated, but their reliability should be investigated. We aimed to assess and compare the reliability of LI-RADS v.2018 and EASL criteria for the diagnosis of HCC using MRI with extracellular contrast agents (ECAs) and gadoxetic acid (GA) and determine the effect of ancillary features on LI-RADS reliability., Approach & Results: Ten readers reviewed MRI studies of 92 focal liver lesions measuring <3 cm acquired with ECAs and GA <1 month apart from two prospective trials, assessing EASL criteria, LI-RADS major and ancillary features, and LI-RADS categorization with and without including ancillary features. Inter-reader agreement for definite HCC diagnosis was substantial and similar for the two contrasts for both EASL and LI-RADS criteria. For ECA-MRI and GA-MRI, respectively, inter-reader agreement was k = 0.72 (95% CI, 0.63-0.81) and k = 0.72 (95% CI, 0.63-0.80); for nonrim hyperenhancement, k = 0.63 (95% CI, 0.54-0.72) and k = 0.57 (95% CI, 0.48-0.66); and for nonperipheral washout, k = 0.49 (95% CI, 0.40-0.59) and k = 0.48 (95% CI, 0.37-0.58) for enhancing capsule. The inter-reader agreement for LI-RADS after applying ancillary features remained in the same range of agreement., Conclusions: Agreement for definite HCC was substantial and similar for both scoring systems and the two contrast agents in small focal liver lesions. Agreement for LI-RADS categorization was lower for both contrast agents, and including LI-RADS ancillary features did not improve agreement., (© 2022 American Association for the Study of Liver Diseases.)

The advent of immunotherapy for patients with hepatocellular carcinoma (HCC) has changed the treatment landscape and conferred a survival benefit on patients with advanced HCC, who typically have a very poor prognosis. The most pronounced improvements in response, as documented by standardized response criteria based on CT or MRI, have been achieved when immunotherapy is combined with other systemic or locoregional therapies. Immune checkpoint inhibitor treatments result in unique patterns on CT and MRI that challenge the application of conventional response criteria such as RECIST, modified RECIST, and European Association for the Study of the Liver criteria. Thus, newer criteria have been developed to gauge therapy response or disease progression for patients receiving immunotherapy, including immune-related RECIST (iRECIST) and immune-modified RECIST (imRECIST), though these remain unvalidated. In this review, we describe the current landscape of immunotherapeutic agents used for HCC, summarize the results of published studies, review the pathobiologic mechanisms that provide a rationale for the use of these agents, and report on the status of response assessment for immunotherapy either alone or in combination with other treatment options. Finally, consensus statements are provided to inform radiologists about essential considerations in the era of a rapidly changing treatment paradigm for patients with HCC.

Background: The aim of the study was to analyze the association between the liver uptake of Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) in the hepatobiliary phase (HBP) in cirrhotic patients and the presence of clinically significant portal hypertension (CSPH), and how these features impact on hepatocellular carcinoma (HCC) detection in the HBP., Patients and Methods: Post-hoc analysis of a prospective cohort of 62 cirrhotic patients with newly US-detected nodule between 1-2 cm (study group). Twenty healthy subjects were used as control group. Qualitative and quantitative analysis of the liver contrast uptake in the HBP assessed by Relative Liver-Enhancement (RLE), Liver-Spleen (LSCR), Liver-Muscle (LMCR), and Liver-Kidney Contrast-Ratio (LKCR), Contrast Enhancement Index (CEI), and Hepatic Uptake (HUI), and biliary excretion, were registered. CSPH was confirmed invasively (HVPG > 10 mmHg) or by indirect parameters. The appearance of HCC at the HBP was analyzed., Results: Nineteen patients (30.6%) did not have CSPH. In 41 patients (66.1%) the final diagnosis was HCC. All indices were significantly higher in the control group, indicating a more intense HBP liver signal intensity compared to patients with cirrhosis, even if the comparison was restricted to patients with no CSPH. CSPH was associated to a lower rate of HCC hypointensity in the HBP (51.9% vs . 85.7% without CSPH, p = 0.004)., Conclusions: Liver uptake of Gd-EOB-DTPA at the HBP is decreased in cirrhosis even if the liver function is minimally impaired and it falls down significantly in patients with CSPH compromising the recognition of hypointense lesions. This fact may represent a limitation for the detection of small HCC in patients with cirrhosis and CSPH., (© 2022 Carla Caparroz, Alejandro Forner, Jordi Rimola, Anna Darnell, Ángeles García-Criado, Juan Ramón Ayuso, María Reig, Jordi Bruix, Carmen Ayuso, published by Sciendo.)

Background & Aims: Recognition of non-characterized liver nodules (NCLN) prior to direct-acting antivirals (DAAs) is associated with increased hepatocellular carcinoma (HCC) risk in patients with HCV. The risk of HCC has not been defined in F3/F4 patients in whom NCLN have been ruled-out before starting DAAs and at sustained virological response (SVR). This study aimed to estimate HCC incidence in this population., Methods: We performed a prospective study including HCV-infected patients with F3/F4 fibrosis, without a history of HCC, and who achieved SVR after DAAs. Patients were only included if they had undergone ultrasound imaging that excluded the presence of HCC/NCLN within 30 days after SVR. All patients were evaluated every 6 months until developing primary liver cancer, death or withdrawal of informed consent. HCC incidence was expressed per 100 patient-years (/100PY). Adherence to screening program was calculated every 6 months for the first 48 months., Results: A total of 185 patients (63/122, F3/F4) were included. Among those with cirrhosis, 92% were Child-Pugh A and 42.7% had clinically significant portal hypertension (CSPH). Albumin-bilirubin score was 1 in 84.9% and 2 in 15.1% of patients, respectively. The median clinical and radiologic follow-up was 52.4 months and 48 months, respectively. Ten patients developed HCC: HCC incidence was 1.46/100PY (95% CI 0.79-2.71) in the whole cohort, 2.24/100PY (95% CI 1.21-4.17) in F4 only and 3.63/100PY (95% CI 1.95-6.74) in patients with CSPH. No HCC was registered in patients with F3. Median time between SVR and HCC occurrence was 28.1 months; 12 non-primary liver cancers were also identified., Conclusions: Patients with cirrhosis without NCLN at SVR remain at risk of HCC development. The absence of HCC in patients with F3 reinforces their marginal cancer risk, but prospective studies are needed to exclude them from screening programs., Lay Summary: Patients with HCV-related cirrhosis, without non-characterized liver nodules at sustained virologic response, remain at risk of hepatocellular carcinoma despite viral cure. However, the cancer risk after successful direct-acting antiviral treatment is marginal in patients with F3 fibrosis without non-characterized liver nodules. If confirmed in larger prospective studies, current screening recommendations may need to be revisited in this group of patients., Competing Interests: Conflict of interest MSZ: received speaker fees from Bayer and travel grants from Bayer, BTG and Eisai; ZM: received consultancy fees from Gilead, Abbvie, Alexion, Orphalan and Deep Genomics; speaker fees from Gilead and Abbvie and research grants from Gilead; SL: received consultancy and speaker fees from Gilead and Abbvie and grants from Gilead, VS: received travel grants from Bayer; GI: received ravel grants from Bayer; NG: congress inscriptions: Eisai; NLL: Bayer, AstraZeneca, Travel funding: Bayer Congress inscriptions: Eisai; AD: speaker fees and travel grants from Bayer; AGC: Speaker fees from BTG and Terumo; AD: speaker fees from Bayer and travel grants from Bayer; SMM: received speaker fees from Bayer and travel grants from Bayer and Eisai; CA: Speaker fees, travel and research grants from Bayer, BTG and Terumo. Consultancy from ROCHE; JR: has consulted for Roche and received speaker fees from Bayer and Roche and travel grants from Bayer; AF: Lecture fees from Bayer, Gilead and MSD; consultancy fees from Bayer, AstraZeneca, Roche and Guerbert; FT: DSMB fees from Archivel Farma, S.L., Daiichi-Sankyo Pharma Development, ArQule and Rovi; speaker fees from Bayer; lecture fees from Janssen; JB: has consulted for Arqule, Bayer-Shering Pharma, Novartis, BMS, BTG- Biocompatibles, Eisai, Kowa, Terumo, Gilead, Bio-Alliance, Roche, AbbVie, MSD, Sirtex, Ipsen, Astra-Medimmune, Incyte, Quirem, Adaptimmune, Lilly, Basilea, Nerviano, Sanofi; and received research/educational grants from Bayer, and lecture fees from Bayer-Shering Pharma, BTG-Biocompatibles, Eisai, Terumo, Sirtex, Ipsen; XF: acted as advisor for Gilead and Abbvie; MR: received consultancy fees and/or travel support from Bayer, BMS, Roche, Ipsen, AstraZeneca, UniversalDX, Boston Scientific and Lilly, lecture fees from Bayer, BMS, Gilead, and Lilly and research grants from Bayer and Ipsen. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: Liver Imaging Reporting and Data System (LI-RADS) for hepatocellular carcinoma (HCC) diagnosis in high-risk patients is a dynamic system, which was lastly updated in 2018. We aimed to evaluate the accuracy for HCC diagnosis of LI-RADS v2018 with magnetic resonance imaging (MRI) with extracellular contrast for solitary nodules ≤ 20 mm detected during ultrasound (US) surveillance in cirrhotic patients, with particular interest in those observations categorized as LI-RADS 3., Methods: Between November 2003 and February 2017, we included 262 consecutive cirrhotic patients with a newly US-detected solitary ≤ 20-mm nodule. A LI-RADS (LR) v2018 category was retrospectively assigned. The diagnostic accuracy for each LR category was described, and the main MRI findings associated with HCC diagnosis were analyzed., Results: Final diagnoses were as follows: 197 HCC (75.2%), 5 cholangiocarcinoma (1.9%), 2 metastasis (0.8%), and 58 benign lesions (22.1%); 0/15 (0%) LR-1, 6/26 (23.1%) LR-2, 51/74 (68.9%) LR-3, 11/12 (91.7%) LR-4, 126/127 (99.2%) LR-5, and 3/8 (37.5%) LR-M were HCC. LR-5 category displayed a sensitivity and specificity of 64% (95% CI, 56.8-70.7) and 98.5% (95% CI, 91.7-100), respectively. Considering also LR-4 as diagnostic for HCC, the sensitivity slightly increased to 69.5% (95% CI, 62.6-75.9) with minor impact on specificity (96.2%; 95% CI, 89.3-99.6). Regarding LR-3 observations, 51 out of 74 were HCC, 2 were non-HCC malignancies, and 20 out of 21 LR-3 nodules > 15 mm (95.2%) were finally categorized as HCC., Conclusions: The high probability of HCC in US-detected LR-3 observations (68.9%) justifies triggering an active diagnostic work-up if intended to diagnose HCC at a very early stage., Key Points: • In cirrhotic patients with nodules ≤ 20 mm detected during US surveillance, 51 out of 74 (68.9%) of LR-3 nodules by MRI corresponded to an HCC. • In LR-3 nodules, HCC diagnosis was closely related to baseline tumor size. All 5 nodules smaller than 1 cm were diagnosed as benign. Oppositely, 20 out of 21 LR-3 observations > 15 mm (95.2%) were diagnosed as HCC. • The high probability of HCC in US-detected LR-3 observations justifies triggering an active diagnostic work-up if intended to diagnose HCC at a very early stage.

Background: Despite atezolizumab and bevacizumab (A + B) is currently the first-line treatment for hepatocellular carcinoma (HCC) patients, some patients will not be adequate for this combination. In the setting of sorafenib some adverse events have been proposed as prognostic factors., Objective: To characterize the early diarrhoea development as prognostic factor in 344 HCC patients., Methods: The development of early diarrhoea in sorafenib treatment defined as patients who developed diarrhoea and needed dose modification within the first 60 days of treatment (e-diarrhoea) and 3-grouping variables were analysed: Patients with e-diarrhoea, patients who developed diarrhoea after the first 60 days of treatment (L-diarrhoea) and patients that never developed diarrhoea (never diarrhoea)., Results: The median overall survival in sorafenib treated patients was significantly different across groups (6.8 months for e-diarrhoea, 26.7 months for L-diarrhoea and 13.3 months for never-diarrhoea). The emergence of e-diarrhoea was associated with poor outcomes (hazard ratio [HR] 1.84 [95%CI 1.15-2.95]), while there was no increased/decreased risk of dismal evolution in patients with L-diarrhoea (HR 0.66 [95%CI 0.42-1.03])., Conclusion: The emergence of e-diarrhoea in HCC patients treated with sorafenib is an early predictor of dismal evolution under this therapy. Thus, prompt identification of these non-responders may be useful for an early switch to second-line therapies., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Goals: To describe the occurrence of malabsorption (MA) in hepatocellular carcinoma (HCC) patients under sorafenib, the potential relationship with pancreatic insufficiency (PI), and the role of pancreatic enzymes supplementation., Background: With the increasing options of second-line systemic therapies for HCC, the recognition of drug intolerance using practical tools is crucial. It has been proposed that a MA syndrome could be due to sorafenib-induced pancreatic dysfunction., Study: All sorafenib-treated patients with suspicion of MA (defined as decreased stool consistency lasting >4 wk or presenting ≥10% body weight loss without HCC progression) were prospectively evaluated by serum markers, endoscopy, and imaging techniques., Results: We evaluated 81 sorafenib-treated patients and 21 developed MA suspicion (85.7% male, 81.5% Child-Pugh A, 52.4% BCLC-B, and 47.6% BCLC-C) within a median 5.9 months after starting sorafenib. The median treatment duration, follow-up, and overall survival after MA suspicion were 5.9, 20.3, and 20.3 months, respectively. Nine of them (42.9%) presented hyperparathyroidism secondary to vitamin D deficiency and 8 with PI. A gradual decrease in pancreatic volume of up to 19% was observed among patients with PI. Six of the 8 patients with PI received pancreatic enzymes, with complete recovery from MA symptoms and stabilization of pancreatic volume., Conclusions: We validated the association between MA and PI in 10% of sorafenib-treated patients. Pancreatic enzymes supplementation successfully led to symptomatic recovery. Awareness of this adverse event can help in the management of sorafenib irrespective of cancer type and likely, of other tyrosine kinase inhibitors for HCC patients., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Immune-checkpoint inhibitors are effective in many advanced tumors. However, there is scarce information regarding the radiological response to these agents in hepatocellular carcinoma outside clinical trials. We aimed to describe the radiological response in a retrospective cohort of hepatocellular carcinoma patients treated with nivolumab and to analyze the radiological evolution according to tumor response at first post-treatment radiological assessment., Methods: We reviewed pre-treatment and post-treatment images (CT or MRI) obtained at different time-points in patients with hepatocellular carcinoma treated with nivolumab outside clinical trials at seven Spanish centers, assessing the response according to RECIST 1.1 and iRECIST and registering atypical responses. We also analyzed the imaging findings on subsequent assessments according to tumor status on the first posttreatment imaging assessment., Results: From the 118 patients with hepatocellular carcinoma treated with nivolumab, we finally analyzed data from 31 patients (71 % Child-Pugh A; 74 % BCLC-C). Median follow-up was 8.39 months [IQR 5.00-10.92]; median overall survival was 12.82 months (95 %CI 10.92-34.79). According to RECIST 1.1, the objective response rate was 16 % and according to iRECIST, the objective response rate was 22.6 %. Findings at the first post-treatment assessment varied, showing stable disease in 44.8 % of patients; findings during follow-up also varied widely, including 4 hyperprogressions and 3 pseudoprogressions., Conclusion: Imaging findings during nivolumab treatment are heterogeneous between and within patients. Progression of disease does not always signify treatment failure, and surrogate end-points may not reflect survival outcomes, making the management of hepatocellular carcinoma patients under immunotherapy challenging., (Copyright © 2020. Published by Elsevier B.V.)

Background and Aims: Hepatic epithelioid hemangioendothelioma is an ultra-rare hepatic vascular tumor, diagnosed more frequently in females. The knowledge about this tumor derives mainly from small case series with sub-optimal treatment outcomes. The aim of this study is to identify the clinical and radiological issues helpful to develop an international prospective registry., Methods: We conducted an international multicentric and retrospective study of patients with hepatic hemangioendothelioma. The clinical, pathological and radiological images collected during follow-up were reviewed. Central radiological revision was performed and 3 patterns of contrast were defined., Results: Between 1994 and 2016, 27 patients with hepatic hemangioendothelioma were identified in three institutions but the final diagnosis was hepatic angiosarcoma in one. The majority were females, median age was 38.7-years and 17 patients were asymptomatic at diagnosis. No patient had Two out of ten (20%) patients had surgical specimens with positive macro-vascular invasion and 50% had extrahepatic disease, and the most frequent pattern was the progressive-central-contrast-uptake. After a median follow-up of 6.7-years, the 5- and 10-year survival rates are 91.5% and 51.9%, respectively., Conclusions: This multicentric study shows the heterogeneous profile of patients with hepatic hemangioendothelioma, reflecting the need to establish a reference network in order to better characterize these patients and ultimately develop a personalized treatment strategy., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Purpose: To assess the effectiveness, safety, and overall survival (OS) of thermal ablation as upfront treatment of intrahepatic colangiocarcinoma (ICC) in patients with cirrhosis., Materials and Methods: This was a retrospective analysis of all biopsy-confirmed ICC in cirrhotic patients treated in the authors' unit from 2001 to 2017. Baseline characteristics, ablation procedures, and complications were recorded, and time to recurrence (TTR) and OS were calculated. Twenty-seven patients were identified. Seventy percent had Child-Pugh A disease, and most had clinically significant portal hypertension. Median tumor size was 21 mm. Twenty-one cases were uninodular, and 10 were single ≤ 2 cm., Results: Complete radiologic necrosis was achieved in 25 cases (92.6%). Median OS was 30.6 months (95% confidence interval [CI], 22.6-46.5), and recurrence was detected in 21 cases (77.8%) with a TTR of 10.1 months (95% CI, 7.7-20.9). In those patients with single ≤ 2-cm ICC, the OS was 94.5 months (95% CI, 11.7-not reached). Differences in OS were statistically significant between patients with single ICC ≤ 2 cm and patients with single ICC > 2 cm (P = .04) and between patients with single ICC > 2 cm and patients with multinodular ICC (P = .02). Only 1 patient had a treatment-related complication., Conclusions: Thermal ablation is a safe and effective treatment for ICC in patients with cirrhosis who are not candidates for surgery. The OS is similar to that reported in surgical series, but the initial treatment success is hampered by a high rate of tumor recurrence. Encouraging long-term survival after thermal ablation is achieved in patients with single ≤ 2-cm ICC., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Tumor heterogeneity in hepatocellular carcinomas (HCC) occurs at different levels. On conventional imaging modalities, the spectrum of tumor heterogeneity is evident in the dynamic enhancement pattern, where the characteristic wash-in and wash-out is present in only 60% of small HCCs. In larger HCCs, heterogeneity within the tumor, known as the mosaic pattern, can reflect the presence of different grades of HCC differentiation. The advent of functional imaging techniques has not improved the diagnostic sensitivity of imaging techniques for the diagnosis of HCC. However, the combination of conventional and functional imaging techniques potentially allows the identification of heterogeneity in tumor vascularity, cellularity, and molecular expression., Competing Interests: Dr. Rimola reports personal fees from Bayer, outside the submitted work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To determine the diagnostic accuracy and predictive value of gadoxetic acid liver MRI (Gd-EOB-DTPA MRI) alone or in combination with diffusion-weighted imaging (DWI) as a second-line tool for detecting early hepatocellular carcinoma (HCC) recurrence in cirrhotic patients with previous HCC treated with resection or ablation., Methods: Between 2014 and 2017, we prospectively included 34 cirrhotic patients with complete response to resection and/or ablation of early HCC in whom a new focal lesion enhancing in the arterial phase without washout was detected during follow-up with EC-MRI. After signing the informed consent, all patients underwent DWI and Gd-EOB-DTPA MRI; two readers analyzed signal intensities on each phase of dynamic study and on DWI. The final diagnosis was established by histology or follow-up EC-MRI. We used cross-tabulation to calculate indices of diagnostic accuracy., Results: We evaluated 34 patients (7 women; 73.5% with hepatitis C virus) with a total of 53 new arterial-phase-enhancing foci (median size, 10 [IQR 9-14] mm). The final diagnosis, reached by histopathology in 15 (35.7%) lesions and EC-MR follow-up in 27 (64.3%), was HCC in 42 (79.2%) and benign conditions in 11 (21.8%). Hepatobiliary-phase hypointensity on Gd-EOB-DTPA MRI plus hyperintensity on DWI yielded 54.8% sensitivity, 90.9% specificity, 95.8% positive predictive value, and 34.5% negative predictive value for diagnosing HCC recurrence., Conclusion: Among potential indices, combining hypointensity on hepatobiliary-phase Gd-EOB-DTPA MRI and hyperintensity on DWI has the highest specificity and positive predictive value to optimally detect HCC recurrence prior to confident diagnosis by conventional imaging criteria on EC-MRI in cirrhotic liver., Key Points: • In patients at risk of HCC recurrence, the use of gadoxetic acid liver MRI and DWI may improve the differentiation of unspecific new arterial-enhancing foci from early hypervascular HCC recurrence in patients with non-conclusive findings on extracellular liver MRI. • Combined findings on hepatobiliary-phase gadoxetic acid-enhanced liver MRI and DWI had high specificity (90.9%) and positive predictive value (95.8%) for detecting early hypervascular HCC recurrence, but limited sensitivity. • Combining hepatobiliary-phase hypointensity on gadoxetic acid MRI and hyperintensity on diffusion-weighted imaging allows early diagnosis of hypervascular hepatocellular carcinoma and may help select patients for salvage therapy.

Background and Aims: Most of the published studies about the diagnostic accuracy of gadoxetic acid-enhanced magnetic resonance (EOB-MR) for the non-invasive diagnosis of hepatocellular carcinoma (HCC) have had a retrospective design. Thus, we aimed to prospectively evaluate the diagnostic accuracy of EOB-MR for the non-invasive diagnosis of HCC in nodules ≤2 cm detected by screening ultrasound (US) in patients with cirrhosis., Methods: Between July 2012 and October 2015, 62 consecutive asymptomatic Child-Pugh A-B cirrhotic patients with newly US-detected solitary nodules between 1 and 2 cm were prospectively included in the study. Hepatic extracellular contrast-enhanced MR (ECCE-MR) followed by EOB-MR were obtained in less than 1-month interval. Two independent radiologists blindly reviewed the EOB-MR studies, and the diagnosis of HCC was assigned when the lesion showed arterial enhancement followed by portal venous phase washout and/or hypointensity on the hepatobiliary phase (HBP). The final HCC diagnosis was made by ECCE-MR according to the accepted non-invasive criteria, or by biopsy in lesions with atypical vascular profile., Results: Final diagnoses were as follows: HCC (n = 41), intrahepatic cholangiocarcinoma (n = 2), colorectal metastases (n = 1) and benign conditions (n = 18). The sensitivity and specificity of EOB-MR for HCC diagnosis were 56.1% (95% CI: 39.7-71.5) and 90.5% (95% CI: 69.6-98.8), respectively, while sensitivity of ECCE-MR was 63.4% (95% CI: 46.9-77.9). The low rate of hypointense HCCs in the HBP and suboptimal liver uptake of contrast agent justify the low sensitivity of EOB-MR for HCC diagnosis., Conclusion: EOB-MR does not surpass the diagnostic accuracy of ECCE-MR for non-invasive diagnosis of HCC in nodules ≤2 cm in cirrhotic patients., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To compare the diagnostic accuracy of extracellular gadolinium-based contrast-enhanced MRI (Gd-MRI) and gadoxetic acid-enhanced MRI (EOB-MRI) for the assessment of hepatocellular carcinoma (HCC) response to locoregional therapy (LRT) using explant correlation as the reference standard., Methods: Forty-nine subjects with cirrhosis and HCC treated with LRT who underwent liver MRI using either Gd-MRI (n = 26) or EOB-MRI (n = 23) within 90 days of liver transplantation were included. Four radiologists reviewed the MR images blinded to histology to determine the size and percentage of viable residual HCC using a per-lesion explant reference standard. Sensitivities, specificities, accuracies, and agreement with histology for the detection residual HCC were calculated., Results: Gd-MRI had greater agreement with histology (ICC: 0.98 [0.95-0.99] vs. 0.80 [0.63-0.90]) and greater sensitivity for viable HCC (76% [13/17 50-93%] vs. 58% [7/12; 28-85%]) than EOB-MRI; specificities were similar (84% [16/19; 60-97%] vs. 85% [23/27; 66-96%]). Areas under ROC curves for detecting residual viable tumor were 0.80 (0.64-0.92) for Gd-MRI and 0.72 (0.55-0.85) for EOB-MRI. Gd-MRI had greater inter-rater agreement than EOB-MRI for determining the size of residual viable HCC (ICC: 0.96 [0.92-0.98] vs. 0.85 [0.72-0.92])., Conclusion: Gd-MRI may be more accurate and precise than EOB-MRI for the assessment of viable HCC following LRT.

Hepatic angiosarcoma and epithelioid hemangioendothelioma (EHE) might be clinically considered a spectrum since, although more frequently presenting indolent behavior, EHE occasionally evolves to high-grade neoplasms. However, in most circumstances, pathological and immunohistochemical patterns define this differential diagnosis. More recently, molecular pathways for angiosarcoma and for EHE from other organs and from soft tissue have been proved different, paving the way for future morpho-molecular assessment of their hepatic counterpart. The frequency of liver involvement by Kaposi sarcoma in HIV-infected patients is lower nowadays. Histological findings and immunostaining for HHV-8 Ag are characteristic. Hepatic small vessel neoplasms have been recently recognized as important mimickers of angiosarcoma. The criteria for this differential diagnosis and the clinical behavior, up to now considered favorable, must be further studied., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

One of the key strategies to improve the prognosis of HCC, beside prevention, is to diagnose the tumor in early stages, when the patient is asymptomatic and the liver function is preserved, because in this clinical situation effective therapies with survival benefit can be applied. Imaging techniques are a key tool in the surveillance and diagnosis of HCC. Screening should be based in US every 6 months and non-invasive diagnostic criteria of HCC based on imaging findings on dynamic-MR and/or dynamic-CT have been validated and thus, accepted in clinical guidelines. The typical vascular pattern depicted by HCC on CT and or MRI consists on arterial enhancement, stronger than the surrounding liver (wash-in), and hypodensity or hyposignal intensity compared to the surrounding liver (wash-out) in the venous phase. This has a sensitivity of around 60% with a 96-100% specificity. Major improvements on liver imaging have been introduced in the latest years, adding functional information that can be quantified: the use of hepatobiliary contrast media for liver MRI, the inclusion of diffusion-weighted sequences in the standard protocols for liver MRI studies and new radiotracers for positron-emission tomography (PET). However, all them are still a matter of research prior to be incorporated in evidence based clinical decision making. This review summarizes the current knowledge about imaging techniques for the early diagnosis and staging of HCC, and it discusses the most relevant open questions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A subset of patients with hepatocellular carcinoma (HCC) beyond Milan criteria might obtain acceptable survival outcomes after liver transplantation. Living donor liver transplantation (LDLT) has emerged as a feasible alternative to overcome the paucity of donors. In 2001, we started a protocol for LDLT in Child A-B patients with HCC fulfilling a set of criteria-the Barcelona Clinic Liver Cancer (BCLC) expanded criteria-that expanded the conventional indications of transplantation: 1 tumor ≤ 7 cm, 5 tumors ≤ 3 cm, and 3 tumors ≤ 5 cm without macrovascular invasion or downstaging to Milan after locoregional therapies. We present a prospective cohort of 22 patients with BCLC extended indications based on size/number (n = 17) or downstaging (n = 5) treated with LDLT between 2001 and 2014. Characteristics of the patients were as follows: median age, 57 years old; males/female, n = 20/2; Child-Pugh A/B, n = 16/6; and alpha fetoprotein < 100 ng/mL, n = 21. Twelve patients received neoadjuvant locoregional therapies. At the time of transplantation, 12 patients had HCC staging beyond Milan criteria and 10 within. Pathological reports showed that 50% exceeded BCLC expanded criteria. Perioperative mortality was 0%. After a median follow-up of 81 months, the 1-, 3-, 5-, and 10-year survival was 95.5%, 86.4%, 80.2%, and 66.8%, respectively. Overall, 7 patients recurred (range, 9-108 months), and the 5-year and 10-year actuarial recurrence rates were 23.8% and 44.4%, respectively. In conclusion, a proper selection of candidates for extended indications of LDLT for HCC patients provide survival outcomes comparable to those obtained within the Milan criteria, but these results need confirmation. Liver Transplantation 24 369-379 2018 AASLD., (© 2017 by the American Association for the Study of Liver Diseases.)

The clinical benefit of sorafenib in patients with hepatocellular carcinoma (HCC) has been undervalued due to the absence of complete responses, even though patients who develop early dermatologic reactions have shown to have a positive outcome. In addition, sorafenib is described as an antiangiogenic drug, but it also acts on immunological cells. Thus, the goal of this study was to assess the complete response rate in a retrospective cohort of HCC patients treated with sorafenib and to describe the profile of the patients who achieve complete response for identifying factors related to this event and their connection with the immunological profile of sorafenib. Ten Spanish centers submitted cases of complete response under sorafenib. The baseline characteristics, development of early dermatologic reactions, and cause of treatment discontinuation were annotated. Radiological images taken before starting sorafenib, at first control, after starting sorafenib, at the time of complete response, and at least 1 month after treatment were centrally reviewed. Of the 1119 patients studied, 20 had been classified as complete responders by the centers, but eight of these patients were excluded after central review. Ten patients had complete disappearance of all tumor sites, and two had just a small residual fibrotic scar. Thus, 12 patients were classified as complete responders (58% HCV, median age 59.7 years, 83.4% Child-Pugh class A, Eastern Cooperative Oncology Group performance status 0 91.7%, and Barcelona Clinic Liver Cancer stage C 83.3%). The median overall survival and treatment duration were 85.8 and 40.1 months, respectively. All but one patient developed early dermatologic reactions, and seven patients discontinued sorafenib after achieving complete response due to adverse events, patient decision, or liver decompensation. Conclusion: Complete response affects 1% of patients with HCC who are treated with sorafenib. The association of complete response with early dermatologic reactions supports the role of a specific immune/inflammatory patient profile in the improved response to sorafenib. (Hepatology 2018;67:612-622)., (© 2017 by the American Association for the Study of Liver Diseases.)

Purpose: To evaluate the diagnostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) with magnetic resonance (MR) imaging for hepatic nodules 20 mm or smaller detected during ultrasonographic (US) surveillance in patients with cirrhosis., Materials and Methods: Between November 2003 and January 2010, patients with cirrhosis with a newly US-detected solitary hepatic nodule 20 mm or smaller were included in this institutional ethics committee-approved study. All patients provided written informed consent before the study; the need to obtain consent for reanalysis of the data was waived. Patients underwent MR imaging and fine-needle biopsy (the reference standard). Nodules without pathologic confirmation were followed up with MR imaging every 6 months. A LI-RADS category was retrospectively assigned to nodules seen at MR imaging. The diagnostic accuracy for each LI-RADS category was described by sensitivity, specificity, and positive and negative predictive values with 95% confidence intervals., Results: Final diagnoses of 133 nodules in 159 patients were as follows: 102 hepatocellular carcinomas (HCCs), three intrahepatic cholangiocarcinomas (ICCs), one neuroendocrine metastasis, and 27 benign lesions (median MR imaging follow-up, 95 months). None (0%) of five LI-RADS category 1 lesions, three (25%) of 12 category 2 lesions, 29 (69%) of 42 category 3 lesions, 24 (96%) of 25 category 4 lesions, and 44 (98%) of 45 category 5 lesions were HCCs. One category 3 lesion was ICC, one category 5 lesion was a neuroendocrine metastasis, and two (50%) of four lesions categorized as other malignancies were HCCs. In patients with nodules detected at surveillance US, LI-RADS category 4 criteria were as effective as category 5 criteria for HCC diagnosis. Combining both categories would improve sensitivity without impairing specificity or positive or negative predictive value for HCC diagnosis (42.3%, 98.2%, 97.8%, and 47.4% vs 65.4%, 96.4%, 97.1%, and 59.6%, respectively)., Conclusion: In patients with cirrhosis with US-detected nodules 20 mm or smaller, both LI-RADS category 4 and category 5 have high specificity for HCC. In addition, a relevant proportion of lesions categorized as LI-RADS category 2 or 3 or as other malignancies were HCCs. Thus, active diagnostic work-up, including biopsy to allow prompt treatment, is recommended in such patients. Online supplemental material is available for this article., (RSNA, 2015)

Background & Aims: Current guidelines recommend diagnostic work-up for nodules >1cm detected during screening for hepatocellular carcinoma (HCC). This implies that patients with benign conditions may undergo unnecessary evaluation and those with small nodules may be intervened too early, leading to overdiagnosis. Since increased arterial vascularization is the hallmark of malignancy, its detection by contrast-enhanced ultrasound (CEUS) could become the signal to proceed with diagnosis confirmation. The aim was to assess if HCCs <2 cm without arterial hyperenhancement by baseline CEUS have a benign evolutionary profile, suggesting that diagnosis and invasive treatment could be delayed until detection of an overt malignant profile, associated with increased vascularization., Methods: We prospectively included 168 cirrhotic patients with a newly detected solitary nodule of 5-20mm by screening ultrasonography. MRI, CEUS and fine needle biopsy (FNB) were performed and if no confident diagnosis was obtained, patients were closely followed to rule out HCC. Final diagnosis was: HCC (n = 119), cholangiocarcinoma (n = 3), neuroendocrine tumour (n = 1) and benign lesions (n = 45)., Results: CEUS did not detect contrast hyperenhancement in the arterial phase in 55 cases (34%). Eighteen out of these 55 nodules were diagnosed as HCC. Non-CEUS hyperenhanced HCCs were more frequently well-differentiated than CEUS-hyperenhanced HCCs (p < 0.004). Fourteen patients were treated with ablation and 4 with resection. Ten (55.6%) patients experienced tumour recurrence after treatment, mostly distant, confirming their overt malignant profile., Conclusions: Absence of contrast hyperenhancement on CEUS during the arterial phase in nodules <2 cm in a cirrhotic liver does not predict a less malignant profile. Accordingly, priority for diagnostic work-up and treatment should not differ according to contrast profiles on CEUS., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Recent advancements have improved the management of patients with liver cancer. Results of studies have informed how to stage and decide the optimal treatment option for each patient with an adequate balance between risks and benefits. The Barcelona Clinic Liver Cancer (BCLC) staging and treatment strategy has been widely endorsed for this purpose. This is not a rigid system: One of the key aspects in the management of patients is the optimal timing for systemic treatment initiation and for declaring tumor progression and/or treatment failure. Some patients at intermediate or even early stage may be considered for systemic therapy as options of higher priority may have failed or may not be feasible. Sorafenib is the sole systemic agent that has shown efficacy in phase 3 trials. Other agents (sunitinib, brivanib, linifanib, everolimus, ramucirumab) have failed in terms of safety and/or survival benefit. Optimal sorafenib administration and adequate adherence of the patients are crucial requirements to obtain the benefits of the drug. Because development of adverse events has been shown to correlate with better outcome, careful dose adjustments should be in place while avoiding unnecessary treatment interruption. Furthermore, recent studies have shown that progression at imaging may not translate in poor prognosis and that treatment beyond progression may be considered if there is no option for a second-line research trial.In this review, the authors examine all of the controversial aspects that affect treatment initiation and maintenance, how response to treatment should be evaluated, and define the needs that are faced by current research., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background & Aims: There are no clinical data/markers to predict improved survival in patients with hepatocellular carcinoma treated with sorafenib. Majority of sorafenib adverse events appear within the first 60 days of treatment and studies correlating them with outcome are needed., Methods: We prospectively studied 147 hepatocellular carcinoma patients (97% cirrhotic, 82% Child-Pugh A, BCLC-B 77, BCLC-C 69) treated with sorafenib. Follow-up included monthly clinical and laboratory monitoring and tumor staging at week 4 and every 8 weeks., Results: After a median follow up of 11.6 months (treatment duration 6.7 months), time to progression and overall survival were 5.1 and 12.7 months. All but one patient presented at least one adverse event (median time to appearance 56 days). Time dependent covariate analysis (HR [95% CI]) identified baseline performance status (2.86 [1.75 to 4.55], p<0.001), BCLC (1.69 [1.18 to 2.50], p = 0.005), and dermatologic adverse event requiring dose adjustment within the first 60 days (0.58 [0.36 to 0.92], p = 0.022) as independent predictors of better outcome. Other early adverse events did not have an impact in outcome. The predictive value of dermatologic adverse events for survival was confirmed by the landmark analysis (p = 0.0270)., Conclusions: Development of dermatologic adverse events within 60 days of sorafenib initiation is associated with better survival. Therefore, this should not to be taken as a negative event and discourage treatment maintenance. Likewise, second line clinical trials should be designed and/or evaluated considering this information to avoid significant bias., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Unlabelled: Sorafenib improves overall survival (OS) of patients with hepatocellular carcinoma (HCC) in the absence of objective response. Thus, time to tumor progression (TTP) is used to capture benefits of novel molecular agents, but proof of its surrogacy with survival is lacking. Furthermore, survival predictors upon progression are not established and there is a need to characterize postprogression survival (PPS) and assess with time-dependent covariates analysis if it is influenced by progression pattern, and not solely by simultaneous impairment of liver function and performance status. We prospectively followed HCC patients treated with sorafenib. Clinical and biochemical evaluation were done every 4 weeks. Radiologic assessment of progression was done at week 4 and then every 8 weeks using RECIST 1.1. The progression pattern was divided into: intrahepatic/extrahepatic increase in tumor size, new intrahepatic lesion, and new extrahepatic lesion (NEH). We included 147 patients (hepatitis C virus [HCV] 57.1%, performance status [PS] 0 83.6%, Child-Pugh A 82.3%, and BCLC-C 47.3%). The median OS was 12.7 months and its independent predictors (hazard ratio [HR], 95% confidence interval [CI]) were: baseline BCLC 2.49 [1.66-3.73], PS 1.86 [1.12-3.10], registration during follow-up of Child-Pugh B or Child-Pugh C scores (2.36 [1.51-3.69] and 2.89 [1.62-5.15], respectively), definitive sorafenib interruption 2.48 [1.54-4.01], and TTP 3.39 [1.89-6.1]. The presence of NEH 2.42 [1.32-4.44] is also an independent predictor of OS and PPS in patients with radiologic progression., Conclusion: Tumor progression is a surrogate of survival but its impact varies according to progression pattern. Thus, PPS is influenced by progression pattern and this is key in prognostic prediction and second-line trial design and analysis., (© 2013 by the American Association for the Study of Liver Diseases.)

Background and Aims: Conventional pathological analysis fails to achieve sufficient sensitivity and specificity for the diagnosis of hepatocellular carcinoma (HCC) in small nodules. Immunohistochemical staining for glypican 3 (GPC3), heat shock protein 70 (HSP70) and glutamine synthetase (GS) has been suggested to allow a confident diagnosis but no prospective study has established the diagnostic accuracy of this approach. The aim of this study is to assess prospectively the diagnostic accuracy of a panel of markers (GPC3, HSP70, GS) for the diagnosis of HCC in patients with cirrhosis with a small (5-20 mm) nodule detected by ultrasound screening., Methods: Sixty patients with cirrhosis with a single nodule 5-20 mm newly detected by ultrasound were included in the study. Contrast-enhanced ultrasound, magnetic resonance and fine needle biopsy of the nodule (gold standard) were performed; the biopsy was repeated in case of diagnostic failures. Three consecutive sections of the first biopsy sample with meaningful material were stained with antibodies against GPC3, HSP70 and GS., Results: Forty patients were diagnosed with HCC. The sensitivity and specificity for HCC diagnosis were: GPC3 57.5% and 95%, HSP70 57.5% and 85%, GS 50% and 90%, respectively. The sensitivity and specificity of the different combinations were: GPC3+HSP70 40% and 100%; GPC3+GS 35% and 100%; HSP70+GS 35% and 100%; GPC3+HSP70+GS 25% and 100%. When at least two of the markers were positive (regardless of which), the sensitivity and specificity were 60% and 100%, respectively. Conventional pathological analysis yielded three false negative results, but the addition of this panel only correctly classified one of these cases as HCC., Conclusion: These data within a prospective study establish the clinical usefulness of this panel of markers for the diagnosis of early HCC. However, the panel only slightly increases the diagnostic accuracy in an expert setting.

Background & Aims: To prospectively assess the diagnostic accuracy of the incorporation of additional magnetic resonance imaging (MRI) parameters in those based on contrast enhancement pattern for the diagnosis of solitary nodules between 5 and 20mm, detected during surveillance in patients with cirrhosis., Methods: Between November 2003 and January 2010, we prospectively included 159 cirrhotic patients with a newly detected solitary nodule between 5 and 20mm in diameter by screening ultrasonography (US). Hepatic MRI and fine-needle biopsy were performed in all patients., Results: Final diagnoses were hepatocellular carcinoma (HCC) (n=103), other malignant lesions (intrahepatic cholangiocarcinoma/metastases) (n=4), and benign lesions (n=52). The specific enhancement pattern (arterial enhancement followed by washout) yielded a sensitivity and specificity of 58.3% and 96.4%, respectively. Peritumoral capsule was present in 43 HCC and in 2 non-HCC lesions. Intralesional fat was detected in 24 nodules; 5 nodules were non-HCC. Finally, the presence of both capsule and fat was observed in 10 cases, all of them HCC (100% specificity), but all of them also displayed the specific enhancement pattern, thus adding no sensitivity or specificity., Conclusions: Conclusive non-invasive diagnosis of HCC in cirrhosis should be based only on the contrast enhancement pattern, while other characteristics at MRI do not increase the diagnostic accuracy., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Imaging techniques play a crucial role in the management of patients with liver cirrhosis in whom a nodular hepatic lesion is detected. The most severe complication of patients with liver cirrhosis is the development of a hepatocellular carcinoma (HCC), and the prognosis of the disease depends on the tumoral stage. Surveillance programs based on ultrasonography (US) are recommended in cirrhotic patients with possibility to be treated if an HCC is detected, in order to improve the patient's survival. Nevertheless, early detection and diagnostic confirmation of HCC remains a challenge despite technological advances. The non-invasive criteria to characterize small HCCs in patients with cirrhosis are based on the evaluation of the vascular profile of the lesion. Dynamic multidetector computed tomography (MDCT) and dynamic magnetic resonance imaging (MRI) are the suitable techniques for this purpose. When diagnosis is not achieved, fine US-guided fine needle biopsy (FNB) is indicated. Cellular-MRI contrast agents may have a role in lesions with atypical vascular pattern in which FNB is not feasible. The assessment of the disease extent is another important goal for imaging techniques. Again, dynamic MDCT and dynamic MRI may be used for staging purposes. Although MRI is more accurate in the detection of additional nodules ranging 1-2 cm, both remain relatively insensitive for the detection of tiny satellite nodules below 1 cm. The therapeutic decision can be made in any particular patient on the basis of the tumoral extension, the liver function, and the general status. After curative and palliative therapeutic procedures, the monitoring of the response is mandatory to decide the next approach: to follow-up, to repeat the treatment, to modify the treatment indication, or to suspend the treatment. In this review, we discuss the most recent information on the imaging of HCC.

Hepatocellular carcinoma (HCC) has a poor prognosis when diagnosed in advanced stages. Patients with cirrhosis of any etiology are a clear risk group. Thus, to improve prognosis, these patients should be included in surveillance programs to detect HCC in the early phases. Ultrasonographic examination is recommended for this purpose. The imaging techniques currently available for characterization of focal liver lesions are dynamic ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT). MRI and CT are also suitable to determine tumoral extension. This article reviews the role of imaging techniques in the diagnosis and study of extension of HCC and in assessment of tumoral response after treatment, according to tumoral stage at diagnosis and the clinical status of the patient., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Most patients with hepatocellular carcinoma (CHC) are not candidates for surgical resection or liver transplantation because of their stage at the time of diagnosis. There are a series of locoregional treatments that achieve a high objective response rate in this group of patients. Percutaneous ablation is considered the best treatment option for CHC (BCLC stage 0/A) not amenable to surgical treatment. In multifocal hepatocellular carcinoma without vascular invasion or extrahepatic extension (BCLC stage B), the only treatment option that has been shown to improve survival in randomized controlled trials is chemoembolization. The evaluation of the effectiveness of these treatments is based on the reduction of viable tumor observed at CT, MRI, or contrast-enhanced US. In this article, we review the indications, technique, and therapeutic efficacy of the different locoregional treatments for CHC., (Copyright © 2009 SERAM. Published by Elsevier Espana. All rights reserved.)

This study assesses the magnetic resonance (MR) features of intrahepatic cholangiocarcinoma (ICC) in patients with cirrhosis with specific analysis of the contrast enhancement pattern. Cholangiocarcinoma may show increased contrast uptake in the arterial phase, and, if washout in the delayed venous phase were to be detected, the noninvasive diagnostic criteria proposed in the American Association for the Study of Liver Diseases guidelines would be refuted. We reviewed the MR findings of 25 patients with cirrhosis with 31 histologically confirmed ICC nodules. Signal intensity on basal T1-weighted and T2-weighted images and characteristics of enhancement after contrast administration on arterial, portal, and delayed phase were registered. Enhancement pattern was defined according to the behavior of the lesions in each phase, and dynamic pattern was described according to the progression of enhancement throughout the different phases. The most frequent pattern displayed by ICC was a progressive contrast uptake (80.6%). Stable contrast enhancement was registered in 19.4%. None of the ICCs showed a washout pattern, a profile that is specific for hepatocellular carcinoma (HCC). The ICC dynamic behavior differed significantly according to tumor size: progressive enhancement pattern was the most frequent (20 of 25 cases) in lesions larger than 20 mm, whereas the stable pattern was mainly identified in nodules smaller than 20 mm. The most characteristic MR contrast pattern in ICC in cirrhosis is a progressive contrast uptake throughout the different phases, whereas contrast washout at delayed phases is not observed. Because stable enhancement pattern without washout also can be registered in small HCC nodules, the evaluation of delayed phase is mandatory for a proper nodule characterization. If washout is not registered, a biopsy should be mandatory for diagnosis.

Background: Evaluation of response to treatment is a key aspect in cancer therapy. Response Evaluation Criteria in Solid Tumors (RECIST) are used in most oncology trials, but those criteria evaluate only unidimensional tumor measurements and disregard the extent of necrosis, which is the target of all effective locoregional therapies. Therefore, the European Association for the Study of the Liver (EASL) guidelines recommended that assessment of tumor response should incorporate the reduction in viable tumor burden. The current report provides an assessment of the agreement/concordance between both RECIST and the EASL guidelines for the evaluation of response to therapy., Methods: The authors evaluated a cohort of 55 patients within prospective studies, including 24 patients with hepatocellular carcinoma who underwent transarterial chemoembolization (TACE) with drug eluting beads (DEB-TACE) and 31 patients who underwent percutaneous ablation (percutaneous ethanol injection [PEI]/radiofrequency [RF]). Triphasic helical computed tomography scans were performed at baseline, at 1 month, and at 3 months after procedure, and 2 independent radiologists evaluated tumor response., Results: Evaluating response according to RECIST criteria, no patients achieved a complete response (CR), 21.8% of patients achieved a partial response (PR) (none in the PEI/RF group), 47.3% of patients had stable disease (SD), and 30.9% of patients had progressive disease (PD). When response was evaluated according to the EASL guidelines, 54.5% of patients achieved a CR, 27.3% of patients achieved a PR, 3.6% of patients had SD, and 14.5% had PD. The kappa coefficient was 0.193 (95% confidence interval, 0.0893-0.2967; P < .0001)., Conclusions: RECIST missed all CRs and underestimated the extent of partial tumor response because of tissue necrosis, wrongly assessing the therapeutic efficacy of locoregional therapies. This evaluation should incorporate the reduction in viable tumor burden as recognized by nonenhanced areas on dynamic imaging studies., ((c) 2008 American Cancer Society.)

Early diagnosis of hepatocellular carcinoma (HCC) in nodules smaller than 2 cm detected by screening ultrasounds becomes essential given that, at that stage, no vascular invasion is usually detected and treatment is associated with a high rate of long-term survival. Improvements in imaging techniques in the last few years have allowed a conclusive diagnosis of HCC in these small nodules without invasive procedures. However, a conclusive diagnosis of HCC by imaging is not always possible and, in more than half of cases, biopsy is needed. On the other hand, histological confirmation of HCC in such tiny nodules is very complex, and in most cases impossible because of the limited sample obtained. In addition, serum tumor markers currently available show low accuracy and are useless for early diagnosis. Progress in the knowledge of molecular mechanisms associated with malignant transformation will allow the use of new techniques that will facilitate diagnosis for HCC in very early stages.

We report on 8 years of imaging and clinical follow-up of a confirmed hepatic angiomyolipoma (AML) undergoing notable growth over this period. The tumor grew considerably in the first 5 years, and its growth especially affected the fatty component; in the last 3 years, growth occurred more slowly. Radiologists should be aware that tumor growth of a hepatic AML can occur.